Developing a stable drug delivery system for the mesoionic compound MIH 2.4Bl using reconstituted high-density lipoproteins (rHDL) nanoparticles




Petty, Roland
Sabnis, Nirupama
Debnath, Dipti
Mathis, James
Zhang, Jinmin
Fudala, Rafal


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Purpose: In recent years, mesoionic compounds have displayed promising results as an anticancer agent due to their unique structure and properties. Specifically, the 1,3-thiazolium-5-thiolate derivative of a mesoionic compound, MIH2.4Bl, has been shown to inhibit oxidative phosphorylation in mitochondria, induce expression of autophagy-related proteins (Beclin-1 and ATG5), and promote cell cycle arrest at the G2/M phase in breast cancer cells. However, due to the hydrophobic nature of the drug, the cellular uptake could be affected. The rHDL drug delivery technology has been successful in solubilizing several drugs. In the present study, we produced a stable rHDL-MIH2.4BI formulation for efficient drug delivery to breast cancer cells. Methods: The rHDL-MIH2.4Bl nanoparticles were prepared using the cholate dialysis protocol enhanced by thermocycling. The size, polydispersity index, and zeta potential of the formulation were determined using a light scattering analysis instrument (Zetasizer, Malvern Panalytical Ltd). Anisotropy was determined by spectrofluorometry, and the entrapment efficiency was determined using the absorbance of MIH2.4Bl at 480nm. Results: rHDL-MIH2.4Bl formulations were successfully prepared with an entrapment efficiency of 20.3%, an average size of 38.7 ± 12.14nm, and a zeta potential of -14.13 ± 0.41mV. After 26 days of storage at 4℃, this formulation retained 97.6% of the drug with an increased anisotropy measurement from 0.189 on day1 to 0.323 on day 26. Conclusions: While additional studies need to be performed to optimize the current formulation, the rHDL-MIH2.4Bl nanoparticle appears suitable to enhance the solubility and bio-availability of MIH2.4Bl.